title: EMMPRIN expression positively correlates with WHO grades of astrocytomas and meningiomas.
abstract: High-grade primary brain tumors possessed poor outcome due to invasiveness. Extracellular matrix metalloproteinase inducer (EMMPRIN) stimulates peri-tumoral fibroblasts to secrete matrix metalloproteinase and promote invasiveness. This study hypothesized that high-grade brain tumors overexpress EMMPRIN. Analyzing the public delinked database from the Gene Expression Omnibus profile, the results showed that the EMMPRIN mRNA level was higher in WHO grade IV (n = 81) than in grade III (n = 19, p < 0.0005) astrocytomas and non-tumor brain tissue controls (n = 23, p < 0.00001). The results of tissue microarray-based immunohistochemical (IHC) staining revealed that EMMPRIN levels positively correlated with WHO grades for astrocytomas (p = 0.008) and meningiomas (p = 0.048). EMMPRIN mRNA levels in conventional glioma cell lines (n = 36) was not less than those in glioma primary culture cells (n = 27) and glioblastoma stem-like cells (n = 12). The GBM8401, U87MG, and LN229 human glioma cell lines also overexpressed EMMPRIN. Hematoxylin and eosin, IHC, and immunofluorescence staining of xenografts confirmed that high-grade brain tumors overexpressed EMMPRIN. Lastly, Kaplan-Meier analysis revealed poorer survival in WHO grade IV (n = 56) than in grade III astrocytomas (n = 21, by log-rank test; p = 0.0001, 95 % CI: 1.842-3.053). However, in high-grade astrocytomas, there was no difference in survival between high and low EMMPRIN mRNA levels. Thus, this study identified that high-grade brain tumors overexpress EMMPRIN, which positively correlates with WHO grades in human astrocytomas and meningiomas, and suggests that EMMPRIN may be a therapeutic target of brain tumor.
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Wen-Chiuan
authors.initials: WC
authors.lastname: Tsai
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Huang
authors.forename: Herng-Sheng
authors.initials: HS
authors.lastname: Lee
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Ma
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Huang
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
authors.forename: Dueng-Yuan
authors.initials: DY
authors.lastname: Hueng
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008577:Meningeal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008579:Meningioma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D060787:Neoplasm Grading; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D014944:World Health Organization
chemical_list: C497886:BSG protein, human; D012333:RNA, Messenger; D051926:Basigin